Glaucoma is a leading cause of blindness both in the US and worldwide. The long-term purpose of this project is to improve functional testing in glaucoma. Assessment and follow-up of patients currently relies on automated perimetry to provide functional testing of the visual field. However, the ability to assess progression and/or response to treatment using perimetry is hampered by high variability, especially in areas of moderate or severe glaucomatous damage. Recent findings by our laboratory and others have advanced our understanding of perimetry by challenging key assumptions about the test. This proposal aims to use these advances to explain and reduce the test variability. This will improve the accuracy, efficiency and utility of current functional testing, giving immediate impact in both research and clinical settings, and laying groundwork for the next generation of instruments and algorithms. The first Specific Aim is to produce an accurate and physiologically justified measure of the Effective Dynamic Range (EDR) of perimetry. It is postulated that the very high contrast stimuli used by perimetry in glaucomatous defects saturate the response of the visual system. The resultant nonlinearity in the contrast-response function would cause the detection probability to asymptote below 100%, explaining the high variability in sensitivities in damaged areas. The limit of the EDR will be defined as the contrast beyond which response linearity cannot be assumed. This will be measured by collecting frequency-of-seeing curves in subjects with moderate or advanced glaucoma. The same technique will be used to determine whether the EDR is extended by use of an increased stimulus size. The second Specific Aim is to derive and test a spatial filter to reduce the variability. This will be the first filter to be based both on sensitivities at other locations in the visual field and on the structure of the optic nerve head. The third Specific Aim is to assess the potential utility of using a linear scale for sensitivity, rather than the current logarithmic decibel scale. First, an efficient linear-scaled thresholding algorithm will be derived and tested, to determine whether it will reduce variability both between tests and in the structure-function relation. Second, linear-scaled global indices of the central visual field will be examined, to determine whether they offer improved prognostic value compared with current decibel-scaled indices when assessing progression. The three aims are complementary. It is anticipated that by combining these aims, variability in perimetry will be better understood, and significantly reduced. Such an improvement in a test as commonly performed as perimetry will significantly impact future clinical practice. PUBLIC HEALTH RELEVANCE: This project aims to explain and reduce the variability observed in functional testing of the visual field in patients with glaucoma. This will allow earlier and more accurate assessment of a patient's current status and response to treatment. It will improve the ability to design an appropriate and cost-efficient personalized management strategy to preserve vision, with the aim of maintaining a patient's quality of life.